Helminthic infections are major health concerns in both tropical and temperate areas of the world. Researchers have consistently found that much of the parasite burden of a population is constrained to a relatively small proportion of individuals, i.e. parasites tend to be overdispersed. The marked predisposition of some individuals to high worm burdens has led international health workers to consider targeting high risk individuals for treatment, since complete eradication is not a realistic goal for soil-transmitted helminths. However, the mechanism for the increased susceptibility of a small segment of the population to high worm loads is not known, although some researchers have suggested that genetic factors may be involved. There are few studies of the genetic determinants of susceptibility to helminthic infections in humans. This project will evaluate the genetic components of susceptibility to helminthic infections using newly developed statistical genetic methods. Specifically, roundworm. hookworm, and whipworm burdens will be measured at two points in time in 1000 members (belonging to 50 pedigrees) of flee Jirel population of eastern Nepal. Hematological (red cell count. white cell count. eosinophil count, hemoglobin. and hematocrit levels) and anthropometric measures (stature, weight, and skinfolds) that are known to reflect response to helminthic infections will also be assessed. Quantitative genetic methods will be used to determine the genetic and environmental components of worm burden and associated biological responses. Pleiotropic genetic effects influencing susceptibility to multispecies helminthic infections will be examined using multivariate genetic methods. The effects of single genes on worm burden or related measures will be assessed using complex segregation analyses. Genetic effects on biological responses to helminthic infection will be tested by examination of the genotype by worm burden interaction effects on host traits such as eosinophil counts. This project will provide new information on the determinants of parasite distribution patterns that will be useful for designing intervention programs.